The recognized similarities between developing embryonic tissues and neoplastic cells have led to a number of experimental demonstrations which indicate that inductive microenvironments can alter the malignant phenotype. In postnatal life a morphogenetic cascade resembling endochondral bone development can be induced by s.c. implantation of demineralized diaphyseal bone matrix. We have examined the ability of this microenvironment to alter the phenotype of the transplantable Swarm rat chondrosarcoma in mixed implants. Neoplastic chondrocytes could be distinguished from host cells by nuclear morphometry since the nuclear area of the neoplastic chondrocytes was 2 to 3 times larger than that of comparable host-derived chondrocytes. Through the first 7 days post-implantation tumor cells in the presence of morphogenetically active matrix are morphologically indistinguishable from those implanted with morphogenetically inactivated matrix or implanted by themselves. With the advent of host cell chondrogenesis, however, adjacent neoplastic cells begin to undergo chondrolysis and calcification. Only those cells in the immediate proximity of host morphogenetic foci appear affected. An average of 26.7 ± 7.0% (SD) of the implant surface areas examined revealed such changes. Chondrosarcoma cells implanted by themselves or in the presence of morphogenetically inactivated bone matrix underwent no such changes. These results suggest that factors released from host cells induced to undergo bone morphogenesis are capable of altering the differentiated phenotype of neoplastic cells.
Supported in part by USPHS Grants CA-35533 and CA-15823 from the National Cancer Institute and a gift to the Department of Pathology from R. J. Reynolds, Inc.